Congenital disorder of deglycosylation 2. Report of a novel MAN2C1 pathogenic variant and additional phenotypic implications

The MAN2C1 gene encodes an enzyme with alpha-mannosidase 2C1 activity, which is responsible for the degradation of defective glycoproteins in the cytoplasm. The purpose of this report is to present a novel MAN2C1 pathogenic variant in a patient with a congenital disorder of deglycosylation 2. We describe a case with 15q24.1q24.3 microdeletion syndrome which also presented a deleterious variant in the MAN2C1 gene located at the opposite allele. We discussed the phenotypic consequences when MAN2C1 gene transcript is missing. • First report of the MAN2C1 c.76_80delTTTAC variant (p.Phe26Argfs*3), producing a truncated 28–amino acid protein with complete loss of function. • The case shows coexistence of a chromosomal microdeletion and a monogenic disorder, explaining phenotypic overlap and supporting personalized care. • This study broadens the phenotype of CDDG type 2 and underscores the value of integrating molecular and clinical data for diagnosis.